The melanocortin (MC) is a group of peptide hormones that are derived from posttranslational modifications by enzymatic cleavage of the preprohormone. The MCs include melanocyte-stimulating hormones (MSH) such as α-MSH, β-MSH and γ-MSH, as well as adenocorticotropic hormame (ACTH). These MCs regulate diverse physiological functions through membrane MC receptors (MC-Rs). Five MC-Rs (MC1-R, MC2-R, MC3-R, MC4-R and MC5-R) have been cloned and characterized. The MC1-R (the first discovered as α-MSH receptor) is expressed in integumental melanocytes and involved in epidermal melanin pigmentation and animal coloration.
Recently, it has been discovered that MC1-R is-involved in pain and inflammation, and MC1-R mRNA is expressed in inflammatory cells such as neutrophils or mononuclear cells. It is likely that MC1-R account for the inhibitory actions of α-MSH on production of nitric oxide in monocytes and migration of neutrophils. Evidence has shown that the α-MSH molecules reduced inflammatory reaction in animal models of inflammatory responses in humans. α-MSH reduced inflammation which was induced in mouse skin by general irritants. Also, α-MSH inhibited mouse paw edema induced by carrageenan. Thus, MC1-R agonists are expected to be useful as a medicament against inflammatory reaction.